Nature Reviews Nephrology最新文献

Engineered CAR macrophages target kidney inflammation 工程化CAR巨噬细胞靶向肾脏炎症

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-27 DOI: 10.1038/s41581-025-00972-z

Susan J. Allison

{"title":"Engineered CAR macrophages target kidney inflammation","authors":"Susan J. Allison","doi":"10.1038/s41581-025-00972-z","DOIUrl":"https://doi.org/10.1038/s41581-025-00972-z","url":null,"abstract":"The administration of anti-inflammatory macrophages has been proposed as an approach to reduce tissue injury in response to inflammation; however, this approach is limited by the instability of macrophages and their potential to switch to a pro-inflammatory phenotype. To overcome these limitations, researchers have now developed a chimeric antigen receptor (CAR) macrophage (CAR-M) that demonstrates anti-inflammatory functions in response to a pro-inflammatory stimulus. “Our approach demonstrates the potential to improve the therapeutic efficacy of immune cells while maintaining a stable and desired phenotype within the inflammatory microenvironment,” states lead author, Qi Cao.Cao and colleagues engineered their CAR construct with an extracellular, anti-TNF single-chain fragment variable (scFv) linked to the intracellular domain of IL-4Rα, such that binding of the anti-TNF scFv to TNF triggered a signal switch to initiate an anti-inflammatory response. “A key innovation of our CAR methodology is the development of a novel chimeric signalling switch receptor (CSSR), which is designed to harness pro-inflammatory signals to drive an anti-inflammatory phenotype within the therapeutic cell,” explains Cao. “Our CSSR approach fundamentally differs from traditional CARs in two critical ways. First, conventional CARs typically augment the existing function of a cell, whereas our CSSR actively switches the cell’s functional output. Secondly, conventional CARs are predominantly used to enhance immune responses, whereas our CSSR is specifically designed to suppress them.”","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"35 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic kidney disease and dementia: an epidemiological perspective 慢性肾脏疾病和痴呆：流行病学观点

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-22 DOI: 10.1038/s41581-025-00967-w

M. Arfan Ikram

{"title":"Chronic kidney disease and dementia: an epidemiological perspective","authors":"M. Arfan Ikram","doi":"10.1038/s41581-025-00967-w","DOIUrl":"https://doi.org/10.1038/s41581-025-00967-w","url":null,"abstract":"Ageing populations worldwide face increasing challenges of multimorbidity (that is, the co-occurrence of two or more chronic conditions). The combination of chronic kidney disease (CKD) and dementia occurs more frequently than it would by simple coincidence, owing to several underlying biological and clinical mechanisms. Population-based cohort studies are an important epidemiological tool and have contributed to improved understanding of these mechanisms. These mechanisms include uniquely shared haemodynamic features of vasculature, overlapping risk factor profiles, and direct neurotoxic effects of accumulating waste products due to poor kidney function. The effect of these pathways is suggested to differ across gender, relevant demographic subgroups, and populations from low- to middle-income countries. Yet, given their study design, population-based cohort studies also inherently face several methodological challenges. These challenges pertain to the use of biomarkers that do not always fully capture the structure and function of the kidney or the brain; bidirectionality across the pathways under study; and practical issues of proper causal inference in light of incomplete distinction between confounders, mediators and effect modifiers. This Review describes our current understanding of the link between CKD and dementia, with a focus on knowledge synthesized from population-based cohort studies. Methodological challenges and possible solutions will be described and directions for future research areas will be outlined.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"92 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The intelligent podocyte: sensing and responding to a complex microenvironment 智能足细胞：感知和响应复杂的微环境

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-08 DOI: 10.1038/s41581-025-00965-y

John F. Bertram, Luise A. Cullen-McEwen, Vinicius Andrade-Oliveira, Niels Olsen Saraiva Câmara

{"title":"The intelligent podocyte: sensing and responding to a complex microenvironment","authors":"John F. Bertram, Luise A. Cullen-McEwen, Vinicius Andrade-Oliveira, Niels Olsen Saraiva Câmara","doi":"10.1038/s41581-025-00965-y","DOIUrl":"https://doi.org/10.1038/s41581-025-00965-y","url":null,"abstract":"Podocytes are key components of the glomerular filtration barrier — a specialized structure that is responsible for the filtration of blood by the kidneys. They therefore exist in a unique microenvironment exposed to mechanical force and the myriad molecules that cross the filtration barrier. To survive and thrive, podocytes must continually sense and respond to their ever-changing microenvironment. Sensing is achieved by interactions with the surrounding extracellular matrix and neighbouring cells, through a variety of pathways, to sense changes in environmental factors such as nutrient levels including glucose and lipids, oxygen levels, pH and pressure. The response mechanisms similarly involve a range of processes, including signalling pathways and the actions of specific organelles that initiate and regulate appropriate responses, including alterations in cell metabolism, immune regulation and changes in podocyte structure and cognate functions. These functions ultimately affect glomerular and kidney health. Imbalances in these processes can lead to inflammation, podocyte loss and glomerular disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"56 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of sex hormone therapy on kidney function 性激素治疗对肾功能的影响

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-05-06 DOI: 10.1038/s41581-025-00966-x

Ellen F. Carney

{"title":"The effects of sex hormone therapy on kidney function","authors":"Ellen F. Carney","doi":"10.1038/s41581-025-00966-x","DOIUrl":"https://doi.org/10.1038/s41581-025-00966-x","url":null,"abstract":"Progression of chronic kidney disease (CKD) is generally faster in cisgender men than cisgender women, suggesting a protective effect of female sex. An observational study in 44 transgender individuals who initiated either feminizing (estradiol and antiandrogens) or masculinizing (testosterone) hormone therapy provides new insights into the effects of sex hormones on the kidney. “This population provides a unique opportunity to study the effects of well-defined changes in sex hormone concentrations,” says researcher Sarah van Eeghen.Sex hormone therapy also resulted in changes in the concentrations of tubular injury biomarkers, with decreases in urinary NGAL, MCP1 and YKL-40 with feminizing therapy and increases in urinary YKL-40 and plasma TNFR1 with masculinizing therapy. “These results suggest that estradiol may protect against early tubular injury and inflammation, whereas testosterone may promote kidney inflammation,” comments van Eeghen. In addition, a plasma proteomics analysis identified several circulating proteins with kidney-protective properties that increased during feminizing therapy and/or decreased during masculinizing therapy. Many of these proteins were positively associated with estradiol and negatively associated with testosterone, including proteins with roles in endothelial function, modulation of inflammation and preservation of kidney structural integrity.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"46 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Implantable bioelectronics and wearable sensors for kidney health and disease 用于肾脏健康和疾病的植入式生物电子学和可穿戴传感器

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-04-29 DOI: 10.1038/s41581-025-00961-2

Surabhi R. Madhvapathy, Soongwon Cho, Elisa Gessaroli, Eleonora Forte, Yirui Xiong, Lorenzo Gallon, John A. Rogers

{"title":"Implantable bioelectronics and wearable sensors for kidney health and disease","authors":"Surabhi R. Madhvapathy, Soongwon Cho, Elisa Gessaroli, Eleonora Forte, Yirui Xiong, Lorenzo Gallon, John A. Rogers","doi":"10.1038/s41581-025-00961-2","DOIUrl":"https://doi.org/10.1038/s41581-025-00961-2","url":null,"abstract":"Established clinical practices for monitoring kidney health and disease — including biopsy and serum biomarker analysis — suffer from practical limitations in monitoring frequency and lack adequate sensitivity for early disease detection. Engineering advances in biosensors have led to the development of wearable and implantable systems for monitoring of kidney health. Non-invasive microfluidic systems have demonstrated utility in the detection of kidney-relevant biomarkers, such as creatinine, urea and electrolytes in peripheral body fluids such as sweat, interstitial fluid, tears and saliva. Implantable systems may aid the identification of early transplant rejection through analysis of organ temperature and perfusion, and enable real-time assessment of inflammation through the use of thermal sensors. These technologies enable continuous, real-time monitoring of kidney health, offering complementary information to standard clinical procedures to alert physicians of changes in kidney health for early intervention. In this Review, we explore devices for monitoring renal biomarkers in peripheral biofluids and discuss developments in implantable sensors for the direct measurement of the local, biophysical properties of kidney tissue. We also describe potential clinical applications, including monitoring of chronic kidney disease, acute kidney injury and allograft health.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"46 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drivers and mechanisms of cognitive decline in chronic kidney disease 慢性肾脏疾病认知能力下降的驱动因素和机制

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-04-25 DOI: 10.1038/s41581-025-00963-0

Giovambattista Capasso, Casper F. M. Franssen, Alessandra F. Perna, Ziad A. Massy, Robert I. Menzies, Carmine Zoccali, Alessandro Tessitore, Maiken Nedergaard, Mark D. Okusa, Alberto Ortiz, Carsten A. Wagner, Robert J. Unwin

{"title":"Drivers and mechanisms of cognitive decline in chronic kidney disease","authors":"Giovambattista Capasso, Casper F. M. Franssen, Alessandra F. Perna, Ziad A. Massy, Robert I. Menzies, Carmine Zoccali, Alessandro Tessitore, Maiken Nedergaard, Mark D. Okusa, Alberto Ortiz, Carsten A. Wagner, Robert J. Unwin","doi":"10.1038/s41581-025-00963-0","DOIUrl":"https://doi.org/10.1038/s41581-025-00963-0","url":null,"abstract":"Cognitive impairment is highly prevalent among individuals with chronic kidney disease (CKD). Despite its high prevalence, the contributing factors and mechanisms underlying brain–kidney dysfunction in CKD remain poorly understood. However, advances in neuroscience, including novel imaging techniques and cognitive assessment methods, have begun to clarify this complex relationship. Several factors contribute directly to cognitive decline in people with CKD, including accumulation of uraemic toxins, microvascular damage, malnutrition, chronic inflammation and disruptions in key neuroprotective pathways, such as those involving Klotho and the glymphatic system. These factors are also linked to the accelerated ageing observed in people with CKD, a key contributor to cognitive decline. However, most studies on cognition in people with CKD have been cross-sectional and associative, offering limited insight into causation. Research advances, such as studies on the effect of uraemic toxins on the blood–brain barrier and the role of the endothelial glycocalyx in vascular damage, offer promising new directions. Emerging data from longitudinal cohort studies are also enhancing our understanding of these processes, with potential implications for both the treatment of CKD-related cognitive decline and the broader issue of cognitive dysfunction in ageing populations. Here, we examine key mechanisms linking CKD to cognitive decline and consider potential therapeutic interventions.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"45 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dialysis and cognitive impairment 透析和认知障碍

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-04-24 DOI: 10.1038/s41581-025-00960-3

Chris W. McIntyre, Arsh Jain

引用次数: 0

Magnetic resonance imaging of renal oxygenation 肾脏氧合的磁共振成像

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-04-23 DOI: 10.1038/s41581-025-00956-z

Thoralf Niendorf, Thomas Gladytz, Kathleen Cantow, Jason M. Millward, Sonia Waiczies, Erdmann Seeliger

{"title":"Magnetic resonance imaging of renal oxygenation","authors":"Thoralf Niendorf, Thomas Gladytz, Kathleen Cantow, Jason M. Millward, Sonia Waiczies, Erdmann Seeliger","doi":"10.1038/s41581-025-00956-z","DOIUrl":"https://doi.org/10.1038/s41581-025-00956-z","url":null,"abstract":"Renal hypoxia has a key role in the pathophysiology of many kidney diseases. MRI provides surrogate markers of oxygenation, offering a critical opportunity to detect renal hypoxia. However, studies that have assessed the diagnostic performance of oxygenation MRI for kidney disorders have provided inconsistent results because MRI metrics do not fully capture the complexity of renal oxygenation. Most oxygenation MRI studies are descriptive in nature and fail to detail the pathophysiological importance of the imaging findings. These limitations have restricted the clinical application of oxygenation MRI and the full potential of this technology to facilitate early diagnosis, risk prediction and treatment monitoring of kidney disease has not yet been realized. Understanding of the relationship between renal tissue oxygenation and MRI metrics, which is affected by kidney size, tubular volume fraction and renal blood volume fraction, and measurement of these factors using novel MR methods is imperative for correct physiological interpretation of renal MR oximetry findings. Next steps to enable the clinical adoption of MR oximetry should involve multidisciplinary collaboration to address standardization of acquisition and data analysis protocols and establish reference values of MRI metrics.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"6 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innate immune cells in acute and chronic kidney disease 先天性免疫细胞在急慢性肾脏疾病中的作用

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-04-22 DOI: 10.1038/s41581-025-00958-x

Xiao-ming Meng, Li Wang, David J. Nikolic-Paterson, Hui-Yao Lan

{"title":"Innate immune cells in acute and chronic kidney disease","authors":"Xiao-ming Meng, Li Wang, David J. Nikolic-Paterson, Hui-Yao Lan","doi":"10.1038/s41581-025-00958-x","DOIUrl":"https://doi.org/10.1038/s41581-025-00958-x","url":null,"abstract":"Acute kidney injury (AKI) and chronic kidney disease (CKD) are inter-related clinical and pathophysiological disorders. Cells of the innate immune system, such as granulocytes and macrophages, can induce AKI through the secretion of pro-inflammatory mediators such as cytokines, chemokines and enzymes, and the release of extracellular traps. In addition, macrophages and dendritic cells can drive the progression of CKD through a wide range of pro-inflammatory and pro-fibrotic mechanisms, and by regulation of the adaptive immune response. However, innate immune cells can also promote kidney repair after acute injury. These actions highlight the multifaceted nature of the way by which innate immune cells respond to signals within the kidney microenvironment, including interaction with the complement and coagulation cascades, cells of the adaptive immune system, intrinsic renal cells and infiltrating mesenchymal cells. The factors and mechanisms that underpin the ability of innate immune cells to contribute to renal injury or repair and to drive the progression of CKD are of great interest for understanding disease processes and for developing new therapeutic approaches to limit AKI and the AKI-to-CKD transition.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"15 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GalNAc-T14-associated defects in B cell homing in IgA nephropathy 与 GalNAc-T14 相关的 IgA 肾病 B 细胞归巢缺陷

IF 41.5 1区医学

Nature Reviews Nephrology Pub Date : 2025-04-22 DOI: 10.1038/s41581-025-00964-z

Susan J. Allison

引用次数: 0